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Purpose To assess the correlation between renal apparent diffusion coefficient(ADC)data obtained from ultra-high b-values and the change of aquaporins in a rat model of type 2 diabetic nephropathy. Methods Thirty male Sprague-Dawley rats were divided into 2 groups:(1)untreated controls(n=15),(2)diabetes(DM)(n=15).Forty days after diabetes induction with streptozotocin,MR imaging was performed in a 7.0-T scanner.All rats received diffusion-weighted imaging(DWI)with 18 b-values(0–4500 s/mm2).Renal apparent diffusion coefficient values were calculated for each of the different anatomical layers of the kidney,and maps of pure diffusion coefficients(D)were calculated from b-values(300-1500),maps of pseudo-diffusion coefficients(D*)were calculated from low b-values(0-200)and maps of ultra-high ADC(ADCuh)were calculated from the ultra-high bvalues(1700-4500).The expression of proteins involved in renal water transport in diabetic rats were then studied by immunohistochemistry microscopy and the mean value of integral optical density(OD)of aquaporins positive signals were measured by applying immune tissue chemistry method.Imaging result,laboratory parameters of diabetic and kidney function,and renal histopathological changes were compared between groups.Correlations between ADCuh and the expression of AQPs were evaluated. Results All diabetic animals developed hyperglycemia.ultra-high ADC was significantly increased in DM animals in the cortex(CO)(0.262±0.050×10-3mm2/s; P<0.001),outer stripe of the outer medulla(OS)(0.240±0.067×10-3mm2/s; P=0.016),inner stripe of the outer medulla(IS)(0.268±0.096×10-3mm2/s; P=0.006)and inner medulla(IM)(0.190±0.101×10-3mm2/s; P = 0.027)compared with control animals(CO,0.196±0.078×10-3mm2/s; OS,0.190±0.088×10-3mm2/s; IS,0.203±0.081×10-3mm2/s; IM,0.140±0.066×10-3mm2/s.while,Between groups,D* and D values were not different.DM rats had an increased OD value of AQP2 in the CO(0.035±0.010; P=0.00)8),OS(0.06±0.019; P=0.011),IM(0.058±0.016; P=0.001),and IM(0.040±0.012; P = 0.009)compared with control animals(CO,0.023±0.010; OS,0.043±0.009; IS,0.036±0.010; IM,0.026±0.011).In contrast,there were no major changes in the abundance of AQP1 and AQP4.ADCuh and OD value of ADP2 expression were positively correlated in CO(P = 0.013,r = 0.500),OS(P = 0.001,r = 0.625),IS(P=0.025,R= 0.456)and IM(P = O.O21,r= 0.467). Conclusion ADCuh may be a useful measurement for noninvasive evaluating kidney damage in diabetic nephropathy,and these changes in ADCuh may reflect function of the AQPs.